title: Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis.
abstract: Ongoing thymopoiesis requires continual seeding from progenitors that reside within the bone marrow (BM), but the identity of the most proximate prethymocytes has remained controversial. Here we take a comprehensive approach to prospectively identify the major source of thymocyte progenitors that reside within the BM and blood, and find that all thymocyte progenitor activity resides within a rare Flk2(+)CD27(+) population. The BM Flk2(+)CD27(+) subset is predominantly composed of common lymphoid progenitors (CLPs) and multipotent progenitors. Of these 2 populations, only CLPs reconstitute thymopoiesis rapidly after intravenous injection. In contrast, multipotent progenitor-derived cells reconstitute the thymus with delayed kinetics only after they have reseeded the BM, self-renewed, and generated CLPs. These results identify CLPs as the major source of thymocyte progenitors within the BM.
authors.affiliation: Stanford Institute of Stem Cell Biology and Regenerative Medicine, CA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Serwold
authors.forename: L I R
authors.initials: LI
authors.lastname: Ehrlich
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000276:immunology; D007700:Kinetics; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
chemical_list: D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C084881:flt3 ligand protein